We further expound on the notion that chronic pain can be reformulated within the context of learning and memory, and demonstrate the relevance of the idea in the design of novel pharmacotherapies. Lastly, we integrate the human and

animal data into a unified working model outlining the mechanism by which acute pain transitions into a chronic state. It incorporates knowledge of underlying brain structures and their reorganization, and also includes specific variations as a function of pain persistence and injury type, thereby providing mechanistic descriptions of several unique chronic pain conditions within a single model. (C) 2008 Elsevier Ltd. All rights reserved.”
“During the past decade, it has been shown that circadian clock genes have more than a simple circadian time-keeping role. Clock genes also modulate motivational DMXAA manufacturer processes and have been implicated in the development of psychiatric disorders such as drug addiction. Recent studies indicate that casein-kinase 1 epsilon/delta (CK1 epsilon/delta)-one of the components of the circadian molecular clockwork-might be involved in the etiology of addictive behavior. The present study was initiated to study the specific role of CK1 epsilon/delta

in alcohol relapse-like drinking using the ‘Alcohol Deprivation Effect’ model. The effect of CK1 epsilon/delta inhibition was tested on alcohol consumption SRT1720 cell line in long-term alcohol-drinking rats upon re-exposure to alcohol Thalidomide after deprivation using a four-bottle free-choice paradigm with water, 5%, 10%, and 20% ethanol solutions, as well as on saccharin preference in alcohol-naive rats. The inhibition of CK1 epsilon/delta with systemic PF-670462 (0, 10, and 30 mg/kg) injections dose-dependently decreased, and at a higher dosage prevented the alcohol deprivation effect, as compared with vehicle-treated rats. The impact of the treatment was further characterized using nonlinear regression analyses on the daily profiles of drinking and locomotor activity. We reveal that CK1 epsilon/delta inhibition blunted the high

daytime alcohol intake typically observed upon alcohol re-exposure, and induced a phase shift of locomotor activity toward daytime. Only the highest dose of PF-670462 shifted the saccharin intake daily rhythm toward daytime during treatment, and decreased saccharin preference after treatment. Our data suggest that CK1 inhibitors may be candidates for drug treatment development for alcoholism. Neuropsychopharmacology ( 2012) 37, 2121-2131; doi:10.1038/npp.2012.62; published online 2 May 2012″
“Sustained vascular smooth muscle contraction can be mediated by several mechanisms, including the influx of extracellular Ca2+ through L-type voltage-gated Ca2+ channels (LTCCs) and by RhoA/Rho-associated kinase (ROCK)-dependent Ca2+ sensitization of the contractile machinery.